TIME-COURSE OF THE INITIAL [CA2-MUSCLE DEPENDS ON [CA2+](E) AND ATP CONCENTRATION(](I) RESPONSE TO EXTRACELLULAR ATP IN SMOOTH)

In response to extracellular application of 50 mu M ATP, all individua l porcine aortic smooth muscle cells respond with rapid rises from bas al [Ca2+](i), to peak [Ca2+](i) within 5 s. The time from stimulus to the peak of the [Ca2+](i) response increases with decreasing concentra tion of ATP. At ATP concentrations of 0.5 mu M and below, the time to the [Ca2+](i) peak varies more significantly from cell to cell than at higher concentrations, and each cell shows complicated initiation and decay kinetics. For any individual cell, the lag phase before a respo nse decreases with increasing concentration of ATP. An increase in lag time with decreasing ATP concentration is also observed in the absenc e of extracellular Ca2+, but the lag phase is more pronounced, especia lly at concentrations of ATP below 0.5 mu M; Whole-cell patch-clamp el ectrophysiology shows that in porcine aortic smooth muscle cells, ATP stimulates an inward current carried mainly by Cl- ion efflux with a t ime course similar to the [Ca2+](i) changes and no detectable current from an ATP-gated cation channel. A simple signal cascade initiation k inetics model, starting with nucleotide receptor activation leading to IP3-mediated Ca2+ release from IP3-sensitive internal stores, fits th e data and suggests that the kinetics of the Ca2+ response are dominat ed by upstream signal cascade components.